Increased Serum miR-206 Level Predicts Conversion from Amnestic Mild Cognitive Impairment to Alzheimer's Disease: A 5-Year Follow-up Study

J Alzheimers Dis. 2017;55(2):509-520. doi: 10.3233/JAD-160468.

Abstract

Evidence suggests that individuals with amnestic mild cognitive impairment (aMCI) tend to progress to probable Alzheimer's disease (AD) with aging. This study was performed to examine whether circulating miRNAs could be potential predictors for the progression of aMCI to AD. A total of 458 patients with aMCI were included in this study, and the clinical data were collected at two time points: the baseline and the follow-up assessment. These aMCI patients were classified into two groups after 5 years: aMCI-stable group (n = 330) and AD-conversion group (n = 128). The expression of miR-206 and miR-132 and the levels of BDNF and SIRT1 in serum were detected using a quantitative real-time RT-PCR (qPCR) and the ELISA method, respectively. Kaplan-Meier method (Log-rank test) was used for univariate survival analysis. Cox proportional hazard model was used to estimate the prognostic value of miRNAs in conversion from aMCI to AD. At the baseline, serum levels of miR-206 in aMCI-AD group were significantly elevated compared to aMCI-aMCI group and the same trend was found at 5-year follow-up time point as well. There were no significant differences in serum levels of miR-132 between the conversion and non-conversion group at both time points. Kaplan-Meier analysis showed significant correlation between AD conversion and higher serum levels of miR-206 for aMCI patients (HR = 3.60, 95% CI: 2.51- 5.36, p < 0.001). Multivariate Cox regression analysis revealed that serum miR-206 and its target BDNF were significant independent predictors for AD conversion (HR = 4.22, p < 0.001). These results suggested that increased serum miR-206 level might be a potential predictor of conversion from aMCI to AD.

Keywords: Alzheimer’s disease; amnestic mild cognitive impairment; circulating microRNA; follow-up study; predictor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / etiology*
  • Brain-Derived Neurotrophic Factor / blood
  • Cognitive Dysfunction / blood*
  • Cognitive Dysfunction / complications*
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • MicroRNAs / blood*
  • Neuropsychological Tests
  • Proportional Hazards Models
  • Sirtuin 1 / blood
  • Survival Analysis
  • Time Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • MIRN206 microRNA, human
  • MicroRNAs
  • SIRT1 protein, human
  • Sirtuin 1